Our proposal investigates molecular messengers that underlie neurotoxic and other actions of drugs of abuse. Specific areas covered in the research plan are neurotoxic influences of nitric oxide signaling, glyceraldehyde-3 -phosphate dehydrogenase and heme oxygenase/biliverdin reductase. Additionally, we will continue studies of D-aspartate as a neuromodulator and mediators of cell stress such as p53, areas which, for the sake of brevity, are detailed separately in the Progress Report.